Time trends in prevalence of p16 positivity and combined HPV/p16 positivity in a large cohort of Danish vulvar cancer patients.

Vulvar cancer is rare, but causes substantial morbidity in affected patients. A subset of vulvar cancers is caused by high-risk human papillomavirus (hrHPV), which primarily exerts its oncogenic effect through upregulation of tumor suppressor protein p16. Tumors positive for both hrHPV and p16 (double positive) are assumed to be HPV-driven, but only few large studies have investigated the combined prevalence of hrHPV and p16 positivity in vulvar cancer over time. In this Danish cross-sectional study, we assessed the prevalence of p16 positivity and double positivity for hrHPV and p16 in a large sample of vulvar squamous cell carcinomas (VSCCs) diagnosed during 1990 to 2017. In a nationwide register, we identified VSCCs from 13 hospitals across Denmark, and collected archival tumor tissue for hrHPV testing with INNO-LiPA and immunohistochemical p16 staining. We calculated the prevalence of hrHPV, p16 positivity and double positivity according to time, age and histological subtype and evaluated time trends through estimated annual percentage changes. We included 1278 VSCCs. Overall, 35.0% (95% confidence interval [CI]: 32.4-37.6) were positive for p16 and 31.0% (95% CI: 28.4-33.5) were positive for both hrHPV and p16. The prevalence of p16 positivity and double positivity increased over time, both in women aged ≤59 and ≥60 years. The double positive prevalence was higher in nonkeratinizing (60.7%) and warty/basaloid VSCCs (67.5%) than in keratinizing (16.1%) and verrucous VSCCs (5.0%). These results indicate that approximately one-third of vulvar cancers were caused by hrHPV infection, supporting a substantial preventive potential of the HPV vaccine.

Long-term outcomes of the global tuberculosis and COVID-19 co-infection cohort.

BACKGROUND: Longitudinal cohort data of patients with tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are lacking. In our global study, we describe long-term outcomes of patients affected by TB and COVID-19. METHODS: We collected data from 174 centres in 31 countries on all patients affected by COVID-19 and TB between 1 March 2020 and 30 September 2022. Patients were followed-up until cure, death or end of cohort time. All patients had TB and COVID-19; for analysis purposes, deaths were attributed to TB, COVID-19 or both. Survival analysis was performed using Cox proportional risk-regression models, and the log-rank test was used to compare survival and mortality attributed to TB, COVID-19 or both. RESULTS: Overall, 788 patients with COVID-19 and TB (active or sequelae) were recruited from 31 countries, and 10.8% (n=85) died during the observation period. Survival was significantly lower among patients whose death was attributed to TB and COVID-19 versus those dying because of either TB or COVID-19 alone (p<0.001). Significant adjusted risk factors for TB mortality were higher age (hazard ratio (HR) 1.05, 95% CI 1.03-1.07), HIV infection (HR 2.29, 95% CI 1.02-5.16) and invasive ventilation (HR 4.28, 95% CI 2.34-7.83). For COVID-19 mortality, the adjusted risks were higher age (HR 1.03, 95% CI 1.02-1.04), male sex (HR 2.21, 95% CI 1.24-3.91), oxygen requirement (HR 7.93, 95% CI 3.44-18.26) and invasive ventilation (HR 2.19, 95% CI 1.36-3.53). CONCLUSIONS: In our global cohort, death was the outcome in >10% of patients with TB and COVID-19. A range of demographic and clinical predictors are associated with adverse outcomes.

Changes in HPV prevalence in Danish women with vulvar cancer during 28 years - A nationwide study of >1300 cancer cases.

OBJECTIVE: A substantial proportion of vulvar cancers are caused by high-risk human papillomavirus (hrHPV), but hrHPV prevalence in vulvar cancer has mainly been investigated in smaller studies which did not evaluate time trends. Our aim was to assess hrHPV prevalence in >1300 Danish vulvar cancers diagnosed during 1990-2017, including changes in hrHPV prevalence over time. METHODS: In a nationwide pathology register, we identified women diagnosed with vulvar cancer at thirteen hospitals from all Danish regions. Archival tumor tissue was collected from local repositories and, upon pathology review, sent to a central laboratory for HPV testing using INNO-LiPA. We calculated hrHPV prevalence according to time, age and histology, and evaluated the overall and age-specific estimated annual percentage change (EAPC). RESULTS: We included 1308 vulvar cancer cases, with a median age of 72 years at diagnosis. The overall hrHPV prevalence was 52.0% (95% CI: 49.3-54.7). HPV types 16/18 were found in 39.6% of cases, whereas nine-valent HPV (9vHPV) vaccine types 16, 18, 31, 33, 45, 52, and 58 were found in 50.8%. The hrHPV prevalence showed an increasing trend over time, with an EAPC of 0.35% (95% CI: 0.00-0.71). The hrHPV prevalence was higher in younger women throughout the study period, and increasing trends over time were seen in both older (age ≥ 60) and younger (age < 60) women. The hrHPV prevalence was higher in non-keratinizing (71.0%) and warty/basaloid (78.0%) carcinomas than in keratinizing (39.4%) and verrucous (36.4%) carcinomas. CONCLUSIONS: Our results indicate that the 9vHPV vaccine could potentially prevent a substantial proportion of vulvar cancers in Denmark.

[Dialogue between bioethics and evidence- based medicine, a narrative ethics perspective]. / Diálogo entre la bioética y la medicina basada en la evidencia, una mirada desde la ética narrativa.

Evidence-Based Medicine (EBM) is the methodological paradigm of Western medicine today. EBM is expected to reduce the use of intuition and to promote the use of scientific evidence, in the clinical decision-making process. Benefits of EBM in clinical practice are thoroughly documented, however, there are also critics. Among other issues, EBM is thought to contribute to an excessive reductionism, to neglect context variables and individual attributes involved in the physician-patient relationship. All the above could lead to several bioethical conflicts. This work consists in a literature review that examines the interaction between EBM and Bioethics in a reciprocity frame, in order to approach possible ethical conflicts that emerge with the use of EBM, and later analyze them from the perspective of the Narrative Ethics model, proposed by the philosopher Paul Ricoeur.

Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Causes of Pruritus in Patients Treated With Immune Checkpoint Inhibitors for Melanomas or Skin Carcinomas.

Background: Pruritus is a frequent adverse event during the use of immune checkpoint inhibitors (ICIs), with a frequency estimated to be between 11 and 47%. The underlying causes remain poorly understood. Objectives: The main goal was to search for putative causes of pruritus occurring in patients treated with ICIs for melanomas and cutaneous carcinomas. Other objectives were to assess the association between the occurrence of pruritus and survival and between the occurrence of pruritus and other adverse events. Methods: A monocentric retrospective descriptive study was performed using data for patients treated with ICIs (nivolumab, pembrolizumab, ipilimumab, and cemiplimab) between August 2010 and November 2019. Results: A total of 181 patients were included (mean age: 69 years). Pruritus was reported by 25 patients (13.8%). We were able to determine three subgroups of pruritus causes under ICI use: pruritus directly related to immunotherapy, pruritus indirectly related through other pruritus-inducing side effects and pruritus unrelated to ICIs. In 6/25 patients, no more specific cause of pruritus was found at the onset of pruritus or in their backgrounds, other than ICI use. Limitations: The study has some limitations due to unicentric and retrospective design. Conclusion: Pruritus was found in 25/181 patients in this series; only in 6/25 patients no potential cause other than ICI could be found, and pruritus was not associated with differences in survival.

Diálogo entre la bioética y la medicina basada en la evidencia, una mirada desde la ética narrativa / Dialogue between bioethics and evidence- based medicine, a narrative ethics perspective

Evidence-Based Medicine (EBM) is the methodological paradigm of Western medicine today. EBM is expected to reduce the use of intuition and to promote the use of scientific evidence, in the clinical decision-making process. Benefits of EBM in clinical practice are thoroughly documented, however, there are also critics. Among other issues, EBM is thought to contribute to an excessive reductionism, to neglect context variables and individual attributes involved in the physician-patient relationship. All the above could lead to several bioethical conflicts. This work consists in a literature review that examines the interaction between EBM and Bioethics in a reciprocity frame, in order to approach possible ethical conflicts that emerge with the use of EBM, and later analyze them from the perspective of the Narrative Ethics model, proposed by the philosopher Paul Ricoeur.

The value of examination of multiple levels of mammary needle core biopsy specimens taken for investigation of lesions other than calcification.

AIMS: It is a standard practice to examine multiple levels of needle core biopsies taken for mammographic calcification, but there is almost no evidence on the value of levels in core biopsies taken for other reasons. This study aimed to assess the value of levels for needle core biopsies taken for investigation of lesions other than calcification. A secondary aim was to assess interobserver agreement of diagnosis. METHODS: For each of the 375 breast core biopsies with three levels the first level was reviewed and a diagnosis made. Then levels 2 and 3 were reviewed and a final diagnosis was made. RESULTS: The diagnosis after examining three levels was different from that in the initial level in 4 of 272 (1.5%, 95% CI 0.04% to 3%) core biopsies taken for reasons other than calcification and in 13 of 103 (13%, 95% CI 6% to 19%) biopsies taken for investigation of calcification. Interobserver agreement of the original diagnosis at the time of reporting and the final diagnosis at the review for this study was 96% (κ 0.947). CONCLUSIONS: This study confirms the value of levels of biopsies taken to investigate mammographic calcification, but suggests that routine levels are of limited value for breast core biopsies taken for other reasons.

Mujer de 20 años con fiebre y neutropenia / Fever and neutropenia in a 20-year-old woman

No disponible

Manejo farmacológico del anciano hospitalizado / Hospitalized pharmacological handling of the old one

Se estudiaron aleatoriamente las historias clínicas de 100 pacientes hospitalizados en salas de medicina del Hosptial Loayza. Se encontró que los pacientes ancianos reciben un promedio de 0.28 medicamentos por patología, antes de su ingreso; y 3.3 medicamentos por patología durante su hospitalización. Los antibióticos y los antihipertensivos fueron fármacos más frecuentemente prescritos, durante la hospitalización. El 18 por ciento de los pacientes estudiados presentaron algún tipo de reacción adversa medicamentosa, siendo severa el 2 por ciento. Las reacciones adversas esperadas y tóxicas (39 por ciento) fueron las más frecuentemente encontradas. En 16 por ciento de pacientes se encontraron interacciones medicamentosas de tipo teórico. Se sugiere incrementar la vigilancia farmacológica en el Hospital Loayza, protocolizar los esquemas de tratamiento; tener en cuenta las insuficiencias del paciente anciano, su estado nutricional, los mecanismos de acción de los fármacos, y las interacciones farmacológicas teóricas de los fármacos utilizados en este tipo de pacientes; mejorar la instrucción sobre la administación de medicamentos y la detección de posibles reacciones adversas. Por ser el Hospital Loayza un hospital de nivel IV, tratar de difundir el uso de técnicas de dosaje de medicamentos, a un costo asequible.

Conocimientos y actitudes de los cirujanos frente a pacientes infectados con los virus de inmunodeficiencia humana, hepatitis B y hepatitis C / Knowledge and attitudes of the surgeons in front of patients infected with the virus of human immunodeficiency, hepatitis B and hepatitis C

La cirugía y el riesgo de adquirir VIH, hepatis B o C, están íntimamente ligados. Los tres virus se transmiten de modo similar. La sangre es el tejido con mayor potencia infectante y el de mayor manipulación en cirugía. La exposición accidental al VIH en trabajadores de salud depende de su profesión, su actitud hacia la bioseguridad y las condiciones de trabajo. El objetivo de este estudio fue determinar los conocimientos y actitudes de los cirujanos del Hospital Loayza (Lima, Perú), respecto a pacientes infectados con VIH, VHB o VHC. Los resultados de este estudio demuestran que 60 por ciento de cirujanos del HAL no conocen su riesgo real de transmisión del VIH, VHB ni VHC. La mayoría de ellos cree estar familiarizado con las precauciones universales y ponerlas en práctica, pero solo la mitad asume una práctica adecuada de bioseguridad. Nuestros cirujanos creen extremar precauciones cuando operan pacientes con estos diagnósticos, pero sus principales precauciones son sólo protector ocular y doble guante. Sólo la tercera parte de ellos está vacunado contra la hepatitis B. Recomendamos elaborar programas educativos y ampliar las prácticas de bioseguridad en centros quirúrgicos y servicios de cirugía, y hacer obligatoria la vacunación contra la hepatitis B.

Comportamiento y características del cáncer ductal in situ en pacientes evaluados en el Instituto Nacional de Enfermedades Neoplásicas durante 1990-1999 / Behavioral and characteristics of the ductal neoplasm in situ in evaluation patients in the Instituto Nacional de Enfermedades Neoplasicas during 1990-1999

El Carcinoma ductal in Situ (DCIS) de la mama es una lesión heterogénea no invasiva de comportamiento distinto según su histología que se origina en la unidad ducto-lobulillar. Su diagnóstico se ha incrementado con el uso de la mamografía hasta llegar a ser un 30-40 por ciento de todas las lesiones malignas de la mama en Estados Unidos, en el Perú representa sólo el 1.7 por ciento. Métodos: Se revisaron todas las historias clínicas de las pacientes con diagnóstico de DCIS operada en el Instituto de Enfermedades Neoplásicas durante 1990-1999. Resultados: Se obtuvieron 83 pacientes que cumplieron los criterios de inclusión, observándose una mediana de 48 años para la edad de presentación y ausencia de antecedentes familiares en un 71.6 por ciento. La mayoría de las mujeres acudieron por presentar síntomas como descarga por el pezón 24.1 por ciento, mastodinea 36.1 por ciento, masa palpable en 71.6 por ciento. El 22.9 por ciento se presentaron sin síntomas. Las lesiones histológicamente fueron no comedocianas en un 72.7 por ciento y de grado nuclear intermedio y bajo en un 90.5 por ciento. La mediana del diámetro tumoral fue de 3 cm. El tratamiento consistió en Mastectomía en 78.3 por ciento y 21.7 por ciento tuvieron cirugía de conservación. Conclusión: El DCIS es una neoplasia heterogénea que debe manejarse individualmente analizando los datos obtenidos clínica, quirúrgica y patológicamente.